Cardiac rupture and aneurysm formation following acute myocardial infarction may be related to degradation of structurally important collagen molecules by inflammatory cell proteolytic enzymes. Using a rat model of acute myocardial infarction, significant collagen degradation was found to occur in the final 24 hours following experimental infarction. This degradation was associated with a marked increase in proteolysis in the infarct region. This collagen degradation was inhibited by eliminating inflammatory cells by prior whole body irradiation. Electron microscopic studies revealed greater preservation of collagen in the 29-hour old infarction of leukopenic rats than in those of controls. These results suggest that there is early collagen degradation after myocardial infarction which is mediated by inflammatory cells and may be of pathogenic importance in the development of cardiac rupture and aneurysm formation.